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(Circulation. 2003;107:1247.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
From the Division of Cardiovascular Diseases and Molecular Medicine Program, Mayo Clinic, Rochester, Minn.
Correspondence to Noel M. Caplice, MD, PhD, Mayo Clinic, GU 1801, 200 First St SW, Rochester, MN 55905. E-mail caplice.noel{at}mayo.edu
Background Recent studies have identified cardiomyocytes of extracardiac origin in transplanted human hearts, but the exact origin of these myocyte progenitors is currently unknown.
Methods and Results Hearts of female subjects (n=4) who had undergone sex-mismatched bone marrow transplantation (BMT) were recovered at autopsy and analyzed for the presence of Y chromosomepositive cardiomyocytes. Four female gender-matched BMT subjects served as controls. Fluorescence in situ hybridization (FISH) for the Y chromosome was performed on paraffin-embedded sections to identify cells of bone marrow origin with concomitant immunofluorescent labeling for
-sarcomeric actin to identify cardiomyocytes. A total of 160 000 cardiomyocyte nuclei were analyzed approximating 20 000 nuclei per patient. The mean percentage of Y chromosomepositive cardiomyocytes in patients with sex-mismatched BMT was 0.23±0.06%. Not a single Y chromosomepositive cardiomyocyte was identified in any of the control patients. Immunofluorescent costaining for laminin and chromosomal ploidy analysis with FISH showed no evidence of either pseudonuclei or cell fusion in any of the chimeric cardiac myocytes identified.
Conclusions These data establish for the first time human bone marrow as a source of extracardiac progenitor cells capable of de novo cardiomyocyte formation.
Key Words: chimera stem cells myocytes, cardiac transplantation, bone marrow
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